This proposal requests funds for a newly available high resolution PET tomograph insert to produce a hybrid MR/PET system allowing true simultaneous acquisition of PET and MR brain imaging data in human subjects. The PET insert will be combined with an existing 3T Siemens TRIO MR system (for which it is specifically designed). The resulting hybrid MR/PET system will be available as a shared resource to researchers at the University of Pittsburgh and other local institutions. Departments within the University that that will benefit from the instrument include: Psychiatry, Radiology & Radiation Oncology, Physical Medicine & Rehabilitation, Neurology & Neurosurgery, Pathology, and Otolararyngology. The system will be sited in the University of Pittsburgh Magnetic Resonance Research Center and will be managed and directed by an Internal Advisory Committee composed of the co-investigators and major users identified in this proposal. The insert uses new PET detector technology, with magnetically insensitive avalanche photodiodes (APDs) in favor of photo-multiplier tubes (PMTs), and consists of a detector ring that fits inside the MR bore. The use of APDs for MR-compatible PET is established in pre-clinical systems for small animal imaging. The proposed insert performs better than present instrumentation for human brain PET imaging, and can operate within the high magnetic field environment without significantly affecting the performance of the MR system. The MR images may be used for attenuation correction of the PET data such that no ionizing radiation is associated with this purpose, as is not the case for PET or PET/CT imaging. The system will provide PET datasets that are intrinsically co-registered with anatomical and functional MR datasets (fMRI, DTI, spectroscopy) in both spatial and temporal domains. Areas where we expect the system to significantly enhance investigational research are: 1) Functional and physiologic validation paradigms (e.g. BOLD MR signal vs. [15O]H2O PET cerebral blood flow). 2) Characterization of the relationship between cognitive function (fMRI) and neuroreceptor occupancy by therapeutic agents and/or an acute pharmacologic challenge (PET). 3) Studies in critical care or ephemeral conditions (e.g. stroke, epilepsy, MS), for which the highly dynamic physiology demands simultaneous anatomical and functional assessments. 4) Precise anatomic delineation and simultaneous functional assessment of brain and head-and-neck tumors for radiation treatment planning, as well as longitudinal assessments of anatomic and functional tumor response. 5) More precise application of structural MR results with respect to atlas-based delineation of brain regions, tissue classification/segmentation, and volumetric assessments. The introduction of multimodality MR/PET systems is expected to have a broad impact on investigational neuroscience and radiation treatment planning and assessment of response in oncology. 11 Major User NIH-funded research projects at the University of Pittsburgh that will immediately benefit from this new multimodality technology are identified. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: [unreadable] [unreadable] [unreadable]